Slide 1

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
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Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 2

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 3

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 4

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 5

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 6

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 7

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 8

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 9

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 10

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 11

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 12

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 13

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 14

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 15

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 16

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 17

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 18

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 19

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 20

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 21

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 22

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 23

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 24

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 25

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 26

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 27

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 28

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 29

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 30

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 31

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 32

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 33

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 34

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 35

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 36

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 37

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 38

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 39

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 40

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 41

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 42

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 43

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 44

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 45

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 46

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 47

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 48

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 49

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 50

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 51

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 52

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 53

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 54

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 55

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 56

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 57

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 58

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 59

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 60

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 61

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 62

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 63

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 64

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 65

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 66

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 67

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 68

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 69

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 70

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 71

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 72

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 73

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 74

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 75

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 76

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 77

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 78

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 79

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 80

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 81

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 82

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 83

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 84

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 85

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 86

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 87

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 88

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 89

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 90

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 91

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 92

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 93

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 94

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 95

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 96

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 97

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 98

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 99

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 100

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 101

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 102

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 103

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 104

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 105

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 106

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 107

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 108

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 109

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 110

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 111

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 112

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 113

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 114

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 115

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 116

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 117

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 118

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 119

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 120

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 121

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 122

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 123

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 124

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 125

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 126

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 127

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 128

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 129

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 130

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 131

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 132

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 133

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 134

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 135

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 136

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 137

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 138

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 139

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 140

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 141

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 142

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 143

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 144

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 145

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 146

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 147

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 148

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 149

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 150

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 151

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 152

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 153

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 154

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 155

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 156

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you


Slide 157

Urinary Tract Infection
Waseem Tayeb,
KKNGH R3

Contents
•
•
•
•
•
•
•
•
•

Definitions
Incidence and epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Antimicrobial therapy
Bladder infection
Kidney infection
Bactreremia, sepsis and septic
shock
• Catheter associated UTI
• UTI in spinal injury Pt

Definitions
• UTI :
An inflammatory response of the urothelium to bacterial
invasion that is usually associated with bacteriuria and pyuria.

• Bacteriuria :
The presence of bacteria in the urine, which is normally free of
bacteria.

• Pyuria:
The presence of white blood cells (WBCs) in the urine,
is generally indicative of infection and an inflammatory
response of the urothelium to the bacterium.

• Bacteriuria without pyuria →bacterial colonization
• Pyuria without bacteriuria → tuberculosis
stones
cancer

Infections defined by their site of origin
• Cystitis
A clinical syndrome of dysuria, frequency,
urgency, and occasionally suprapubic pain.

• Acute pyelonephritis
An acute bacterial infection of the kidney.

• Chronic pyelonephritis
Describes a shrunken, scarred kidney, diagnosed
by morphologic, radiologic, or functional evidence
of renal disease that may be postinfectious

• UTIs definition in terms of functional status
of the urinary tract and the health of the host.
• Uncomplicated UTI :
An infection in a healthy patient with a structurally
and functionally normal urinary tract.

• A complicated infection
Associated with factors that increase the chance of
acquiring bacteria and decrease the efficacy of
therapy

Functional or anatomic abnormality of urinary tract
Male gender
Pregnancy
Elderly

Diabetes
Immunosuppression
Childhood UTI
Recent antimicrobial agent use
Indwelling urinary catheter
Urinary tract instrumentation
Urinary tract instrumentation
Symptoms for more than 7 days at presentation

• UTIs defined by their relationship to other UTIs.
First or isolated infection:
An individual who has never had a UTI or has one remote from a
previous UTI.

Unresolved infection:
One that has not responded to antimicrobial therapy.

Recurrent infection:
One that occurs after successful resolution of an antecedent infection.

Reinfection :
Describes a new event associated with reintroduction of bacteria into
the urinary tract from outside.

INCIDENCE AND EPIDEMIOLOGY

• Account for:
>7 million visits to physicians' offices
>1 million complicate office visits
1 million emergency department visit
100,000 hospitalizations annually
1.2% of all office visits by women
0.6% of all office visits by men

•

Surveys screening for bacteriuria in female :
1% of schoolgirls have bacteriuria
4% by young adulthood
1% to 2% per decade of age

• The prevalence of bacteriuria in
women has been estimated at 3.5%,
and increasing with age in a linear
trend
• 30% of 24 y women with symptomatic
UTI requiring antimicrobial therapy
• Half of all women will experience a
UTI during their lifetime.
• Bacteriuria in young women is 30
times >men.
• with increasing age, the ratio of
women to men progressively
decreases.
• 20% of women and 10% of men older
than 65 years have bacteriuria

PATHOGENESIS

• UTIs are a result of interactions between the uropathogen and
the host.

 Successful infection of the urinary tract is
determined by
The virulence factors of the bacteria,
The inoculum size
The host defense mechanisms.

• Routes of Infection :
 Ascending Route:
Bowel reservoir
Adherence to the introital and
urothelial mucosa

 Hematogenous Route:
Uncommon
Secondarily infected in patients

 Lymphatic Route:
Occur in unusual circumstances,
such as:
Severe bowel infection
Retroperitoneal abscesses..

Urinary Pathogens
 community-acquired infections :
E. coli accounting for 85%
gram-negative Enterobacteriaceae,(Proteus and Klebsiella,)
gram-positive (E. faecalis and S. saprophyticus)

 Nosocomial infections
E. coli, accounting for 50%
Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas
aeruginosa, Providencia, E. faecalis, and S. epidermidis
Gardnerella vaginalis, Mycoplasma species, and Ureaplasma
urealyticum may infect patients with intermittent or indwelling
catheters

 Anaerobes in the Urinary Tract
The distal urethra, perineum, and vagina are normally colonized by
anaerobes.
Anaerobic organisms are frequently found in suppurative infections
of the genitourinary tract.
Bacteroides species, including B. fragilis, Fusobacterium species,
anaerobic cocci, and Clostridium perfringens

 Mycobacterium tuberculosis and Other NonTuberculous Mycobacteria
 Chlamydia

Bacterial Virulence Factors
• play a role in determining the ability of an organism to invade the
urinary tract and level of infection within the urinary tract.
• uropathogenic E. coli (UPEC), can infect the urinary tract by the
expression of virulence factors that enable them to adhere to and
colonize the perineum and urethra and migrate to the urinary tract
where they establish an inflammatory response in the urothelium.
• A recent genomic analysis of a UPEC strain revealed the presence
of genes for putative chaperone-usher that may function as
adhesins, toxins, proteases, invasins, serum resistance factors, or
motility mediators

 Early Events in UPEC Pathogenesis
• Bacterial Adherence
Bacterial adherence is a specific interaction that plays a role in
determining the organism, the host, and the site of infection.
• This interaction is influenced by:
The adhesive characteristics of the bacteria,
The receptive characteristics of the epithelial surface
The fluid bathing both surfaces.

• UPEC expresses a number of adhesins that allow it to attach to urinary
tract tissues
• classified as either fimbrial or afimbrial,

• A typical piliated cell may contain 100 to 400 pili. The pilus is usually 5 to
10 nm in diameter, is up to 2 μm long,
• Pili are defined functionally by their ability to mediate hemagglutination
of specific types of erythrocytes.
• The most well-described pili are types 1, P and S.

 Type 1 (Mannose Sensitive) Pili:
• Expressed on both nonpathogenic and pathogenic E. coli
• Facilitate bacterial colonization of the vaginal mucosa and bladder.
• These pili mediate hemagglutination of guinea pig erythrocytes
• The reaction is inhibited by the addition of (mannoseMSHA)
• Consist of a helical rod composed of repeating FimA subunits joined
to a 3-nm wide distal tip structure containing the adhesin FimH

• Binding of the FimH adhesin to mannosylated host receptors on the
uroepithelium → colonization of E. coli in the vaginal introitus,
urethra, and bladder and cause cystitis
• The luminal surface of the bladder is lined by umbrella cells.
appear as a quasi-crystalline array of hexagonal complexes
composed of four integral membrane proteins known as uroplakins
• Two of the uroplakins, UPIa and UPIb, can specifically bind UPEC
expressing type 1 pili.

 P (Mannose Resistant) Pili:
• Found in most pyelonephritogenic strains of UPEC
• Mediate hemagglutination of human erythrocytes that is not altered
by mannose (MRHA)
• The adhesin PapG, at the tip of the pilus, recognizes the α-dgalactopyranosyl-(1-4)-β-d-galactopyranoside moiety present in the
globoseries of glycolipids which are found on P-blood group
antigens and on uroepithelium .
• Other Adhesins:
 S pili: which bind to sialic acid residues via the SfaS adhesin,
It is associated with both bladder and kidney infection
 F1C pili: bind to glycosphingolipids in renal epithelial cells and
induce an interleukin-8 inflammatory response

• Epithelial Cell Receptivity
 Vaginal Cells:
•

E. coli strains that cause cystitis adhere more to epithelial cells from
susceptible women

•

The increased bacterial adherence was also characteristic of buccal
epithelial cells.

•

A small variation in both vaginal cell and buccal cell receptivity from day to
day

•

premenopausal women susceptible at certain times during the menstrual
cycle and early pregnancy

•

Uropathogens attached in larger numbers to uroepithelial cells from women
> 65 years

• Blood group antigens are important part of the uroepithelial cell
membrane.

• women with Lewis blood group Le(a−b−) and Le(a+b−)
(nonsecretor) phenotypes have higher incidence of recurrent UTIs
than women with Le(a−b+) phenotype
• The protective effect in women with the Le(a-b+) phenotype may be
due to fucosylated structures at the vaginal cell surface or in the
overlying mucus which decreases availability of putative receptors
for E. coli

 Bladder Cells
• the initial step in the intricate cascade of events leading to UTIs
is fimH-mediated binding to the bladder epithelium

• FimH binds mannosylated residues on the uroplakin molecules
covering bladder superficial epithelial cells.

• UPEC Persistence in the Bladder:
• After attachment to the epithelium, UPEC is quickly internalized into

the bladder superficial cells → establish a new niche to protect
itself from the host innate immune response
• Once intracellular, the UPEC organisms rapidly grow and divide

within the cell cytosol → small clusters of bacteria(early
intracellular bacterial communities IBCs )
• As they grow, the bacteria maintain their typical rod shape of 3 μm
and form a loosely organized cluster, with microorganisms randomly
oriented in the cell cytoplasm.
• Between 6 to 8 hours after inoculation, early IBCs show a drop in

→

bacterial growth rate
doubling times greater than 60 minutes, a
significant shortening of the bacterial morphology to of 0.7 μm,

→ a biofilm-like community

• Biofilms shield bacteria from antimicrobial agents and the host
immune response by:
Slower growth rate of the bacteria
Expression of factors that inhibit antimicrobial activity,
Inability of the antimicrobial agent to penetrate the biofilm
Protects the bacteria from neutrophils because they are unable
to effectively penetrate the IBC and engulf the bacteria.

• Bacteria on the edge of IBCs eventually detach then escape the
host cell into the bladder lumen (fluxing) to readhere and reinvade
superficial cells →second IBC formation.

Natural Defenses of the Urinary Tract
 Periurethral and Urethral Region:
• The normal flora usually contain microorganisms such as
lactobacilli, coagulase-negative staphylococci, corynebacteria, and
streptococci that form a barrier against uropathogenic colonization.
• Changes in the vaginal environment related to estrogen, cervical
IgA, and low vaginal pH may alter the ability of bacteria to
colonize.

 Urine
• The most inhibitory factors :
- Flow of urine and voiding  #1 defense
- High osmolality with a low pH inhibitory to bacterial growth
- High urea and organic acid content can reduce survival of
bacteria within the urinary tract
- Uromodulin (Tamm-Horsfall protein), saturating all the
mannose-binding sites of the type 1 pili, →blocking bacterial
binding to the uroplakin receptors of the urothelium
- Lactoferrin within urine: can scavenge essential iron away
from bacteria

 Bladder
• Factors responsible for defense :
- The ability of the bladder to empty
- Innate and adaptive immunity
•
- Exfoliation of epithelial cells.

Immune Response:
• mediated by a series of pathogen-associated molecular pattern
receptors (PAMPs),
 Toll-like receptors (TLRs) :
• provide the link between recognition of invading organisms and
development of the innate immune response.
• TLRs are conserved among many species of pathogens, such as
(LPS) and peptidoglycan (PG),
• activate signaling pathways that initiate immune and inflammatory
responses to kill pathogens.
• TLR4 expressed on Superficial bladder epithelial cells with CD14

→ recognize LPS from the bacteria and → the innate immune
response
• TLR11 expressed on uroepithelial cells → recognizes UPEC and
protects the kidneys from ascending infection cells

Alterations in Host Defense Mechanisms
Obstruction
Vesicoureteral Reflux
Underlying Disease
Diabetes Mellitus
Renal Papillary Necrosis
Human Immunodeficiency Virus
Pregnancy
Spinal Cord Injury with High-Pressure Bladders

CLINICAL MANIFESTATIONS

Symptoms and Signs

Diagnosis
• Urine Collection:
 Voided and Catheterized Specimens
• Men:
Circumcised men→no preparation.
Not circumcised,→ the foreskin should be retracted and the
glans penis washed with soap and then rinsed with water before
specimen collection.
• Women: contamination with introital bacteria and WBCs is common,
•
•
•
•

The first 10 mL of urine: urethra
Midstream specimen bladder
Prostatic fluid
First 10 mL after massage

 catheteraization
 Suprapubic Aspiration

Urinalysis
• Sediment from an approximately 5- to 10-mL specimen
obtained by centrifugation for 5 minutes at 2000 rpm is
analyzed.
• Bacteriuria, Pyuria, and Hematuria

 Bacteriuria:
• Microscopic bacteriuria →105 colony-forming units (cfu) per milliliter
of urine
• The bacterial count must be approximately 30,000/mL before
bacteria can be found in the sediment, stained or unstained, spun or
unspun
False-negative :
Early infection due to low no of bacteria and WBCs
Diluted samples
False-positive:
Contamination of the urine specimen collection.

 Pyuria :
• Examining the centrifuged sediment or using a hemocytometer to
count the number of WBCs in the unspun urine.
• 1 to 2 WBCs per high-power field (HPF) in sediment from a
centrifuged specimen = 10 WBCs/mm3 in an unspun specimen.
• > 2 WBCs per HPF in a centrifuged specimen or 10 WBCs/mm3 of
urine correlates well with the presence of bacteriuria and is rarely
seen in nonbacteriuric patients

 Hematuria :
• Microscopic hematuria is found in 40% to 60% of cases of cystitis
and is uncommon in other dysuric syndromes
 Nitrites: formed when bacteria reduce the nitrate present in urine
 Leukocyte esterase : sensitivity of 75% to 96% in detecting pyuria
associated with infection

Urine Culture:
Two techniques:
A: Direct surface plating of urine on split-agar
disposable plates.
- Blood agar G+tive – G-tive bacteria
- Desoxycholate or eosin–methylene
blue (EMB) G-tive
• 0.1 mL of urine onto each half of the plate.
• Overnight incubation,
• The number of colonies multiplied by 10 to
report the number of cfu per milliliter of urine.

Urine must be refrigerated immediately on
collection and should be cultured within 24
hours of refrigeration.

B: The dip slides
• Soy agar (a general nutrient agar to grow all
bacteria) on one side and EMB or
MacConkey’s agar on other.
•

A slide is dipped into urine, the excess is
allowed to drain off, and the slide is replaced
in its plastic bottle and incubated.

•

The volume of urine that attaches to the slide
is between 1/100 mL and 1/200 mL.

• the colony count is 100 to 200 times the
number of colonies that become visible with
incubation.

IMAGING TECHNIQUES

 Plain Film of the Abdomen
• Radiopaque calculi
• Gas patterns
• Absent psoas or abnormal renal contour, perirenal or renal abscess

 Plain Film Renal Tomograms
• Small or poorly calcified stones despite overlying gas
• Struvite and uric acid stones that contain small amounts of calcium
may be seen

 Excretory Urogram
• Useful to determine the exact site and extent of urinary tract
obstruction
• Not the best screening test for hydronephrosis, pyonephrosis, or
renal abscess
• Unnecessary for routine evaluation

 Voiding Cystourethrogram
• Neuropathic bladders
• Female patient who has a urethral diverticulum causing her
persistent infections
• VUR

 Ultrasonography
• Useful in r/o hydronephrosis associated with UTI,
pyonephrosis, and perirenal abscesses
• No radiation or contrast agent risk

 CT and MRI
• Best antomic detail
• More sensitive than IVP or U/S for acute focal bacterial
nephritis and renal and perirenal abscesses
• MR: advantages in delineating extrarenal extension of
inflammation

 Radionuclide Studies
Gallium-67
• used to distinguish
some upper tract from
lower tract infections
• possible mechanisms:
– concentration within
labeled PMNs
– leakage of proteinbound gallium
through capillaries
– increased
vascularity of the
lesion
• can see focal bacterial
nephritis and infected
renal cysts

Indium-111
- Indium 111–labeled WBC
accumulate only in sites of
inflammation and not in normal
kidneys or tumors
- highly specific for inflammation

PRINCIPLES OF
ANTIMICROBIAL THERAPY

• Efficacy of the antimicrobial therapy is critically
dependent on:
- The antimicrobial levels in the urine
- The duration that this level remains above the minimal
inhibitory concentration of the infecting organism
• Resolution of infection is closely associated with the
susceptibility of the bacteria to the concentration of the
antimicrobial agent achieved in the urine
• The concentration of the antimicrobial agent achieved in blood
is not important in treatment of uncomplicated UTIs.

• In renal insufficiency, dosage modifications are necessary for agents
that are cleared primarily by the kidneys
•

In renal failure, the kidneys may not be able to concentrate an
antimicrobial agent in the urine; →difficulty in eradicating bacteria
may occur.

• A decision regarding the antimicrobial selection and
the duration of therapy must consider:
- The spectrum of activity of the drug against the pathogen
- Uncomplicated or complicated,
- Potential adverse effect
- Cost.

Bacterial Resistance

 Inherited chromosomal resistance
• Exists in a bacterial species because of the absence of the proper
mechanism on which the antimicrobial agent can act.
• Proteus and Pseudomonas species are always resistant to
nitrofurantoin .

 Acquired chromosomal resistance
• Selection of resistant mutants within the urinary tract during therapy
• Resistant organism (clone) was present before, but only in one per
105 to 1010 organisms
• The remainder of the bacteria, which are susceptible to the
administered antimicrobial agent, will be eradicated by therapy, but
within 24 to 48 hours a repeat urine culture will show high bacterial
counts of the resistant mutant.
• This phenomenon is most likely to occur when the antimicrobial
level in the urine is close to or below the minimal inhibitory
concentration of the drug

 Extrachromosomal-mediated resistance
•

Acquired and transferable via plasmids, which contain the genetic
material for the resistance, called R-factor resistance

• Much more common
• Produces multiply resistant strains, making therapy more difficult
• Occurs only in the fecal flora, never within the urinary tract
• Patients previously exposed to β-lactams, aminoglycosides,
sulfonamides, TMP, and tetracycline will often have R-factor
resistance to both the antimicrobial agent to which the bacteria
were exposed and also to other antimicrobial agents.

Drug or Drug Class

Mechanism of Action

Mechanisms of Drug Resistance

β-Lactams penicillins,
cephalosporins, aztreonam

Inhibition of bacterial cell wall
synthesis

-Production of β-lactamase
- Alteration in binding site of
penicillin-binding protein
- Changes in cell wall porin
size (decrease penetration)

Quinolones

Inhibition of bacterial DNA
gyrase

- Mutation in DNA gyrasebinding site
- Changes in cell wall porin
size (decrease penetration)
Active efflux

Aminoglycosides

Inhibition of ribosomal protein
synthesis

- Downregulation of drug
uptake into bacteria
- Bacterial production of
aminoglycoside-modifying
enzymes

Nitrofurantoin

Inhibition of several bacterial
enzyme systems

- Not fully elucidated-develops
slowly with prolonged
exposure

Trimethoprimsulfamethoxazole

Antagonism of bacterial folate
metabolism

Draws folate from
environment (enterococci)

Vancomycin

Inhibition of bacterial cell wall
synthesis (at different point
than β-lactams)

Enzymatic alteration of
peptidoglycan target

Antimicrobial Formulary
Reliable Coverage of Antimicrobials Used in the Treatment of
UTIs of Commonly Encountered Pathogens :
Antimicrobial Agent or Class

Gram-Positive Pathogens

Amoxicillin or ampicillin

Streptococcus
Enterococci

Amoxicillin with clavulanate

Staphylococcus (not MRSAEnterococci)

First-generation cephalosporins

Streptococcus
Staphylococcus (not MRSA)

Gram-Negative Pathogens
Escherichia coli
Proteus mirabilis
P. mirabilisHaemophilus influenzae,
Klebsiella species
E. Coli
P. Mirabilis
Klebsiella species

Second-generation cephalosporins
(cefamandole, cefuroxime , cefaclor )

Streptococcus

E. coli, P. mirabilis

Third-generation cephalosporins
(ceftriaxone)

Streptococcus
Staphylococcus (not MRSA)

Most, excluding P. aeruginosa

Third-generation cephalosporins
(ceftazidime )

Streptococcus

Most, including P. aeruginosa

Antimicrobial Agent or Class

Gram-Positive Pathogens

Gram-Negative Pathogens

Aminoglycosides

Staphylococcus (urine)

Most, including P. aeruginosa

Fluoroquinolones

Streptococcus*

Most, including P. aeruginosa

Nitrofurantoin

Staphylococcus (not MRSA)
Enterococci

Many Enterobacteriaceae (not
Providencia, Serratia, Acinetobacter)
Klebsiella species

Trimethoprim-sulfamethoxazole

Streptococcus
Staphylococcus

Most Enterobacteriaceae (not P.
aeruginosa)

Vancomycin

All, including MRSA

None

ANTIMICROBIAL
PROPHYLAXIS FOR COMMON
UROLOGIC PROCEDURES

Host Factors That Increase the Risk of Infection
Advanced age
Anatomic anomalies
Poor nutritional status
Smoking
Chronic corticosteroid use
Immunodeficiency
Chronic indwelling hardware
Infected endogenous/exogenous material
Distant coexistent infection
Prolonged hospitalization

 Urethral Catheterization and Removal
• The risk of infection after one-time urethral catheterization is
1% to 2% in healthy domiciliary women
• Prolonged use of an indwelling urethral catheter in hospitalized
patients

↑ risk of bacterial colonization

- 3% to 10% incidence of bacteriuria per catheter day
- 100% incidence of bacteriuria with long-term (>30 days)
• Prophylactic administration of antimicrobial agents during
catheterization is not generally recommended because of
bacterial resistance

• Special Considerations
Patients with Risk of Endocarditis
• The urinary tract is the second most common site of entry of
organisms that cause endocarditis.
• The risk of endocarditis after urologic procedures is low
• Enterococcus faecalis (enterococci) is the most common
organism causing endocarditis after urologic procedures
• Prophylaxis is recommended for both high- and moderate-risk
patients.

• Prophylaxis should be initiated for urologic procedures, including
- obstructed urinary tract
- prostatic surgery
- urinary reconstruction with intestine
- percutaneous renal surgery
- cystoscopy, and urethral dilation

• Moderate-risk patients include other
congenital malformations

 Patients with Indwelling Orthopedic Hardware

BLADDER INFECTIONS

Uncomplicated Cystitis
Risk Factors for UTIs
Reduced Urine Flow

urethral stricture, foreign body (calculus)

Outflow obstruction, prostatic hyperplasia, prostatic Neurogenic bladder
carcinoma,

Inadequate fluid uptake (dehydration)

Promote Colonization

Sexual activity-increased inoculation

Spermicide-increased binding

Estrogen depletion-increased binding

Antimicrobial agents-decreased indigenous flora

Catheterization

Facilitate Ascent

Urinary and Fecal incontinence

Residual urine with ischemia of bladder wall

 Clinical Presentation
• Dysuria, frequency or urgency, and suprapubic pain Hematuria
or foul-smelling urine may develop.
• Fever, chills, and other signs of dissemination are not present.
(superficial infection of bladder mucosa),
• suprapubic tenderness

 causative organism :
• 75% to 90%
• 10% to 20%

E. coli
S. saprophyticus,

 Laboratory Diagnosis
•
•
•
•

pyuria :
sensitivity 95%
and specificity 70%.
bacturia :
sensitivity 40-70% and specificity 85- 95%,
Dipsticks: nitrite or leukocyte esterase
Urine culture -/+

 Management
Antimicrobial Selection
Circumstanc
es

Route

Drug

Dosage
(mg)

Frequency
per dose

Duration
(days)

500 mg
500 mg
1 doublestrength tablet
(160-800 mg)
400 mg

BID
QD
BID

3

Women
Healthy

Oral

Ciprofloxacin
Levofl oxacin
TMP-SMX

Norfloxacin

BID

Symptoms for
>7 days, recent
UTI, age >65 yr,
diabetes,
diaphragm use

TMP-SMX or
Fluoroquinolo
ne

As above

As above

7

Pregnancy

Amoxicillin
Cephalexin
Nitrofurantoin
macrocrystals
TMP-SMX*

250 mg
500 mg
As above

TID
QID
As above

7

As above

As above

Men
Healthy and age
<50 yr

Oral

TMP-SMX
Fluoroquinolone

As above

As above

7

7

 Follow-Up
• young asymptomatic → no Follow-up.
• older women or men
culture

→ urinalysis, and urine

Asymptomatic Bacteriuria
• Women : Two consecutive voided urine specimens with isolation of
the same bacterial strain in quantitative counts of 105 cfu/mL
• Men: A single clean-catch voided specimen with similar counts is
adequate.
• Catheter : A single catheterized urine specimen with a solitary
isolate with a quantitative count of 102 cfu/mL identifies bacteriuria in
women or men

Prevalence of Asymptomatic Bacteriuria in Selected
Populations
Population

Population

Prevalence, %

Prevalence, %

Healthy, premenopausal women

1.0-5.0

Elderly persons in a long-term care facility

Pregnant women

1.9-9.5

Women

25-50

Postmenopausal women aged 50-70 years

2.8-8.6

Men

14-50

Diabetic patients
Women

Patients with spinal cord injuries
9.0-27
Intermittent catheter use

Men

0.7-11
Sphincterotomy and condom catheter in
place

Elderly persons in the community
Women

10.8-16

Men

3.6-19

Patients undergoing hemodialysis

23-89

28

57

Patients with indwelling catheter use
Short-term

9-23

Long-term

100

• Management :
Observation
Screening for and Treatment of Asymptomatic Bacteriuria
Premenopausal nonpregnant women

Not recommended

Pregnant women

Recommended

Diabetic women

Not recommended

Older persons residing in the community

Not recommended

Elderly institutionalized subjects

Not recommended

Subjects with spinal cord injuries

Not recommended

Patients with indwelling urethral catheters

Not recommended

Urologic interventions
Immunocompromised patients and
transplant patients

Recommended
Not recommended

Complicated Cystitis
• infection in a compromised urinary tract or caused very resistant
pathogen .
Complicating Host Factors
Functional/structural abnormalities of urinary tract
Recent urinary tract instrumentation
Recent antimicrobial agent use
Diabetes mellitus
Immunosuppression
Pregnancy
Hospital-acquired infection

 Treatment of Complicated UTIs

Common Pathogens

E. coli, Proteus species, Klebsiella
species, Pseudomonas species,
Serratia species, enterococci,
staphylococci

Mitigating Circumstances

Recommended Empirical
Treatment

Mild-to-moderate illness, no
nausea or vomiting-outpatient
therapy

Oral* norfloxacin , ciprofloxacin,
or ofloxacin for 10-14 days

Severe illness or possible
urosepsis- hospitalization
required

Parenteral† ampicillin and
gentamicin, ciprofloxacin,
levofloxacin , ceftriaxone,
aztreonam , ticarcillin-clavulanate
or imipenem-cilastin until fever
gone; then oral* trimethoprimsulfamethoxazole, norfloxacin ,
ciprofloxacin, or levofloxacin for
14-21 days

Unresolved UTIs
Body_ID: HC008102

•

inadequate initial therapy eliminate symptoms and/or bacterial
growth in the urinary tract.
Causes of Unresolved Bacteriuria, in Descending Order of Importance
Bacterial resistance to the drug selected for treatment
Development of resistance from initially susceptible bacteria
Bacteriuria caused by two different bacterial species with mutually exclusive susceptibilities
Rapid reinfection with a new, resistant species during initial therapy for the original susceptible
organism
Azotemia
Papillary necrosis from analgesic abuse
Giant staghorn calculi in which the "critical mass" of susceptible bacteria is too great for antimicrobial
inhibition
Self-inflicted infections or deception in taking antimicrobial drugs (a variant of Munchausen's
syndrome)

• Initial empirical antimicrobial agent different from the
original agent Fluoroquinolones for 7 days.

Recurrent UTIs
• Reemergence of bacteria from a site within the urinary tract
(bacterial persistence) or new infections from bacteria outside
the urinary tract (reinfection).

 Bacterial persistence :
• Caused by the same organism
• Close intervals
• Cured by identification, removal or correction of the focus

Correctable Urologic Abnormalities That Cause Bacterial Persistence
Infection stones

Unilateral medullary sponge kidneys

Chronic bacterial prostatitis

Nonrefluxing, normal-appearing, infected ureteral
stumps after nephrectomy

Unilateral infected atrophic kidneys

Infected urachal cysts

Ureteral duplication and ectopic ureters

Infected communicating cysts of the renal calyces

Foreign bodies

Papillary necrosis

Urethral diverticula and infected periurethral glands Perivesical abscess with fistula to bladder

 Reinfections :
• Caused by different species.
• Long intervals
• No an alterable urologic abnormality → medical management.
• women and girls : ascending from the bowel flora.
• Men: associated with a urinary tract abnormality.
Risk factors
Evidence of upper tract infections

Fistula,

History of unexplained hematuria,

Analgesic abuse

Obstructive symptoms,

Severe disease

Neurogenic bladder dysfunction,

Diaphragm-spermicide

Renal calculi,

Postmenopausal women,

 Antimicrobial management :
• Indicated in women ≥ 2 UTIs over 6-month or ≥ 3 UTIs within a 12month involves:
Low-dose continuous prophylaxis,
Self-start intermittent therapy
Postintercourse prophylaxis.

 Low-Dose Continuous Prophylaxis:
• Oral antimicrobial agents with minimal adverse effects on the bowel
and vaginal flora and do not cause bacterial resistance
(1) Nitrofurantoin, 50 to 100 mg half-strength (HS)
(2) TMP-SMX, 40 to 200 mg
(3) TMP, 50 mg
(4) Keflex, 250 mg
• Monitoring for infections every 1 to 3 months, even in asymptomatic
patients.
• Breakthrough infections usually respond to full-dose therapy with the
drug used for prophylaxis

 Self-Start Intermittent Therapy
• The patient is given a dip slide device to culture the urine and is
instructed to perform a urine culture when symptoms of UTI occur
• A broad spectrum antibiotics with minimal or no side effects on the
bowel flora.
• Fluoroquinolones are ideal

 Post-intercourse Prophylaxis
• Nitrofurantoin, Cephalexin, TMP-SMX, or a fluoroquinolone taken as
a single dose, will effectively reduce the incidence of reinfection

KIDNEY INFECTIONS

Acute Pyelonephritis
 Clinical Presentation:
• Abrupt onset of chills, fever (100° F or greater)
• unilateral or bilateral flank
• Accompanied by dysuria, increased urinary frequency, and
urgency.

 Laboratory Diagnosis:
• Blood tests:
• leukocytosis with a predominance of neutrophils,

•
•

↑ESR
↑ C-reactive protein levels

• elevated creatinine
• creatinine clearance may be decreased.
• Blood cultures may be positive.( 25% uncomplicated )

• Urinalysis usually :
• The presence of large amounts of
granular or leukocyte casts in the
urinary sediment is suggestive of
acute pyelonephritis.
• Bacteriology:
- E. coli 80% of cases.
- Proteus, Klebsiella, Pseudomonas,
Serratia, Enterobacter, or
Citrobacter should be suspected in
patients with recurrent UTIs, are
hospitalized, or have indwelling
catheters, as well as in those who
required recent urinary tract
instrumentation
- Gram-positive bacteria rarely cause
pyelonephritis.

Brightfield micrograph of a mixed bacterial leukocyte
cast from patient with acute pyelonephritis. Only the
bacteria and the nucleus of a leukocyte stain
strongly. Many bacteria are clearly demonstrated by
through-focusing (toluidine blue O stain,
magnification ×640). (From Lindner LE, Jones RN,
Haber MH: A specific urinary cast in acute
pyelonephritis. Am J Clin Pathol 1980;73:809-811.)

 Radiologic Findings:
• Excretory Urogram:
• Renal enlargement, (most common)
• An overall length of 15 cm or a
length 1.5 cm greater than the
unaffected side has been
established as a criterion for the
diagnosis of renal enlargement in
acute pyelonephritis
• The calyces have an attenuated or
spidery appearance.
• Calyceal and ureteral dilation (the
bacte-rial endotoxins that impair
ureteral peristalsis).

A, Excretory urogram. Ten-minute film demonstrates enlarged right
kidney with minimum function. Findings are consistent with edema.
B, Ultrasound of the right kidney demonstrates renal enlargement,
hypoechoic parenchyma, and compressed central collecting
complex (arrows). (From Schaeffer AJ: Urinary tract infections. In
Gillenwater JY, et al [eds]: Adult and Pediatric Urology.
Philadelphia, Lippincott William & Wilkins, 2002, pp 211-272.)

• Renal Ultrasonography and Computed Tomography:
• used :
Complicated UTIs
Not respond after 72 hours of therapy
• Renal enlargement,
• Hypoechoic or attenuated parenchyma and a compressed collecting
system.

 Pathology :
• The parenchyma shows a focal, patchy infiltrate of neutrophils.
• Bacteria are often in the infiltrate.
Early: limited to the interstitium
Later: linear bands extend from the papillae to the cortex
• Abscesses may cause tubular destruction;
• The glomeruli are usually spared.

 Management:
• Initial Management.
Subdivided into :
(1) Uncomplicated infection :

Not warrant hospitalization

(2) Uncomplicated infection : Ill patient with normal urinary tracts
warrant hospitalization
(3) Complicated infection
•

: Associated with hospitalization,
catheterization, urologic surgery,
or urinary tract abnormalities

• Risk factors associated with increased risk of death
or hospitalization:
•
•
•
•
•
•
•
•

Advanced age,
Septic shock,
Bedridden status,
Immunosuppression,
Recent antibiotic use,
Diabetes mellitus,
Long-term urinary catheterization
A change in initial antimicrobial therapy

Circumstances
Outpatientmoderately ill, no
nausea or vomiting

Route
Oral

Drug
TMP-SMX

Dosage
160 to 800 mg

Frequency per
Dose
BID

Ciprofloxacin

500 mg

BID

Levofloxacin

500 mg

QD
7

Norfloxacin
400 mg

Inpatient-severely
ill, possible sepsis

Parenteral

Duration (days)
10-14

BID

TMP-SMX

160 to 800 mg

BID

Ampicillin and
gentamicin

1g
1.5 mg/kg

QD
TID

Ciprofloxacin

400 mg

Levofloxacin

500 mg

Ceftriaxone

1 to 2 g

14

BID
QD
QD

Take until afebrile,
then take oral
TMP-SMX or
fluoroquinolone
Pregnant

Parenteral

Ceftriaxone

1 to 2 g

Ampicillin and
gentamicin

1g

Aztreonam

1g

Take until afebrile,
then take:
Oral

Cephalexin

QD

QD
14
TID-QID

500 mg

BID

Acute Focal or Multifocal
Bacterial Nephritis
• An uncommon, severe form of acute renal infection in which a heavy
leukocyte infiltrate is confined to a single renal lobe (focal) or
multiple lobes (multifocal).

 Clinical Presentation:
• Similar but more severe.
• 50% of the patients are bacteremic

 Radiologic Findings:
• IVP :
• Poorly marginated mass
• The mass has slightly less
nephrographic density than the
surrounding normal renal parenchyma.
• Ultrasonography :
• poorly marginated sonolucent with lowamplitude echoes that disrupt the
cortical medullary junction

• CT contrast :
• Wedge-shaped areas of decreased
enhancement

Acute focal bacterial nephritis. A, Excretory urogram. Five-minute
tomogram demonstrates normally functioning upper and lower poles
and a poorly marginated midrenal mass with poor function and absent
collecting system visualization. B, Ultrasound; longitudinal view of the
left kidney demonstrates spleen (S) and left kidney (arrows). Note
irregular midpole mass (M) of slightly higher echo texture than
surrounding normal renal parenchyma. C, Contrast medium-enhanced
CT scan demonstrates a wedge-shaped area of low density (arrows)
in the middle portion of the left kidney. The findings resolved after
antimicrobial therapy.

 Management:
• Hydration and IV antimicrobial agents for at least 7 days,
followed by 7 days of oral antimicrobial therapy.
• Follow-up studies will show resolution of the wedge-shaped
zones of diminished attenuation.
Failure to respond to antimicrobial therapy :
• Rule out obstructive uropathy,
• Renal or perirenal abscess,
• Renal carcinoma
• Acute renal vein thrombosis.

Emphysematous Pyelonephritis
• An acute necrotizing parenchymal and perirenal infection
caused by gas-forming uropathogens.
• Considered a complication of severe pyelonephritis rather than a
distinct entity.

 Pathogenesis:
• Usually occurs in diabetic patients,
• High tissue glucose levels provide the substrate for microorganisms
such as E. coli, which are able to produce carbon dioxide by the
fermentation of sugar.
• Impaired host response caused by local factors, such as obstruction,
or a systemic condition, such as diabetes, allows organisms
producing carbon dioxide to use necrotic tissue to generate gas

 Clinical Presentation:
• Severe, acute pyelonephritis
• A chronic infection precedes the acute attack. Some time
• Classic triad:
Fever
Vomiting
Flank pain
• Pneumaturia is absent unless the infection involves the collecting
system.

 Radiologic Findings:
• The diagnosis is established
radiographically.
KUB:
• A crescentic collection of gas over the
upper pole of the kidney
• Gas extends to the perinephric space and
retroperitoneum. (progression)

•
•
•
•

Emphysematous pyelitis Vs pyelonephritis
Air is in the collecting system
Secondary to a gas-forming bacterial UTI,
Nondiabetic patients

plain film. Extensive perinephric (long arrows) and
intraparenchymal (short arrows) gas secondary to
acute bacterial pyelonephritis. (From Schaeffer AJ:
Urinary tract infections

• Excretory urography
• Not recommended (abnormal renal
function)

• Ultrasonography
• Focal echoes suggesting the
presence of intraparenchymal gas
• CT scan:
• Define the extent of the
emphysematous process and
guiding management
• A nuclear renal scan
• Assess the degree of renal function
impairment

A, CT scan of the right kidney shows complete destruction with
gas (arrowheads) extending beyond the renal fascia. B, CT
scan with a modified lung window display shows the
characteristic streaky gas in the completely destroyed kidney.
The patient died on arrival in the emergency department

.

 Management :
• Emphysematous pyelonephritis is a surgical emergency.
• Most patients are septic
• Fluid resuscitation and broad-spectrum antimicrobial therapy
• Functioning kidney:
• Medical therapy can be considered.
• Nephrectomy if not improve after a few days of therapy
• Nonfunctioning kidney:
• Not obstructed → nephrectomy.
• Obstructed

→ catheter drainage

• If improved → nephrectomy may be deferred

Renal Abscess
• A collection of purulent material confined to the renal parenchyma.
• Hematogenous gram-positive abscess (past)
• Gram-negative organisms (majority)
Ascending infection associated with tubular obstruction from prior
infections or calculi appears to be the primary pathway
 predisposing factors:
• Complicated UTIs associated with stasis, calculi, pregnancy,
neurogenic bladder, and diabetes mellitus

 Clinical Presentation
•
•

fever, chills, abdominal or flank pain,
and occasionally weight loss and malaise.

 Radiologic Findings :
• Ultrasonography :
•

low-echodensity space-occupying lesion
with increased transmission

Acute renal abscess. Transverse ultrasonographic scan of the right
kidney demonstrates a poorly marginated rounded focal hypoechoic
mass (arrows) in the anterior portion of the kidney

• CT contrast scan:
•

Initially :
- Renal enlargement and focal,
rounded areas of decreased
attenuation

• Later :
- A thick fibrotic wall begins to form
around the abscess.

Acute renal abscess. Nonenhanced CT scan through the mid pole of
the right kidney demonstrates right renal enlargement and an area of
decreased attenuation (arrows). After antimicrobial therapy, a followup scan showed complete regression of these findings.

• Chronic:
- Obliteration of adjacent tissue
planes
- Thickening of Gerota's fascia
- A round or oval parenchymal
mass of low attenuation
- The ring sign is caused by the
increased vascularity of the
abscess wall
Chronic renal abscess. A, Enhanced CT scan shows an irregular septated
low-density mass (M) extensively involving the left kidney. Note thickening of
perinephric fascia (arrowheads) and extensive compression of the renal
collecting system. Findings are typical of renal abscess. B, Ultrasound
longitudinal scan demonstrates a septated hypoechoic mass (M) occupying
much of the renal parenchymal volume

 Management :

• The classic treatment for an abscess has been percutaneous or
open incision and drainage (>5 cm)
•

Evidence that the intravenous use of antimicrobial agents and
careful observation of a small abscess less than 3 cm in diameter

• CT- guided needle aspiration may be necessary to differentiate an
abscess from a hypervascular tumor.
• Empirical antimicrobial therapy

• Hematogenous:
penicillin , cephalosporin or vancomycin.
• Gram-negative
Third-generation cephalosporins, antipseudomonal penicillins, or
aminoglycosides
• ≥5 cm in immunocompromised hosts or those that do not respond to
antimicrobial therapy should be drained percutaneously

Infected Hydronephrosis and
Pyonephrosis
• Infected hydronephosis :
Bacterial infection in a hydronephrotic
kidney.

• pyonephrosis :
Infected hydronephrosis associated with
suppurative destruction of the
parenchyma of the kidney with loss of
renal function
 Clinical Presentation :
• Very ill ppatient,
• High fever, chills, flank pain, and
tenderness.
• History of urinary tract calculi, infection, or
surgery is common.

Pyonephrosis-gross specimen. The kidney shows marked
thinning of the renal cortex and medulla, suppurative
destruction of the parenchyma (arrows), and distention of
the pelvis and calyces. Previous incision released a large
quantity of purulent material. The ureter showed
obstruction distal to the point of section

• Radiologic Findings
• U/S :
• Infected hydronephrosis:
internal echoes within the
dependent portion of a dilated
pyelocalyceal system.

•

pyonephrosis :
Focal areas of decreased
echogenicity are seen within the
hydronephrotic parenchyma.

Pyonephrosis. A, Longitudinal ultrasound scan of the right
kidney demonstrates echogenic central collecting complex
(C) with radiating echogenic septa (arrows) and thinned
hypoechoic parenchyma. Multiple dilated calyces (o) with
diffuse low-level echoes are seen.

 Management :
• Antimicrobial drugs and drainage of the infected pelvis.
• A ureteral catheter to drain the kidney
• Percutaneous nephrostomy tube insertion.

Perinephric Abscess
 Route :
• Rupture of an acute cortical abscess into the perinephric space
• Hematogenous seeding from sites of infection.
Bowel perforation,
Crohn's disease
Spread of osteomyelitis from the
thoracolumbar spine
• E. coli, Proteus, and S. aureus account for most infections

• paranephric abscess:
A perinephric infection ruptures through
Gerota's fascia into the pararenal space

Left, Normal anatomic relationships of
structures surrounding the kidney.
Right, Anatomic differences seen in
subcapsular (A) and perirenal (B)
processes. In perirenal abscesses, the
abscess fluid extends outside the renal
capsule, thus causing the capsular
artery and renal fascia to deviate away
from the kidney. These findings may be
seen in radiologic studies.

 Clinical Presentation :
•
•
•
•

Similar to that of pyelonephritis
One third of patients may be afebrile.
An abdominal or flank mass.
Should be suspected in a patient with UTI and abdominal or flank
mass or persistent fever after 4 days of antimicrobial therapy.

 Laboratory features :
•
•
•
•

Leukocytosis,
↑creatinine,.
Urine cultures
Blood culture

 Radiologic Findings :

Nonenhanced CT scan through the lower pole of the right
kidney (previous left nephrectomy) shows extensive
perinephric abscess. Extensive abscess (A) distorts and
enlarges the renal contour, infiltrates perinephric fat
(straight arrows), and also extends into the psoas muscle
(asterisk) and the soft tissues of the flank (curved arrow).
Also note that normal renal collecting system fat has been
obliterated by the process.

Perinephric abscess involving the right adrenal gland. CT
scan shows large right pararenal mass (arrows) with
multiple low-density areas within. At surgery, a large
pararenal abscess with extensive involvement of the right
adrenal was found

.

 Management :
• The primary treatment for perinephric abscess is drainage Vs
nephrectomy
• Percutaneous drainage contraindicated in large abscess cavities
filled with thick, purulent fluid.
• Antimicrobial therapy.
An aminoglycoside together with an antistaphylococcal agent

Chronic Pyelonephritis
 Clinical Presentation :
•
•

No symptoms until →renal insufficiency,
Symptoms of chronic renal failure.

• History of recurrent of acute pyelonephritis,
Intermittent symptoms of fever, flank pain, and dysuria may be
elicited.

 Radiologic Findings :
• pyelographic findings
• Asymmetry and irregularity of the
kidney outlines,
• Blunting and dilation of calyces
• Cortical scars
•

In advanced pyelonephritis,
Calyceal distortion and irregularity
together with cortical scars
complete the picture.

Chronic pyelonephritis. Ten-minute excretory
urogram demonstrates irregular renal outline
with upper pole parenchymal atrophy. Note
significant loss of renal cortical thickness over
blunted and dilated calyces. Lower pole mass
(M) is a simple cyst. (From Schaeffer AJ:
Urinary tract infections.

• Pathology :
Gross:
• kidney is often diffusely contracted, Y-shaped scar, and pitted.
• The parenchyma is thin, and the corticomedullary demarcation is
lost.
Histology:
• An interstitial infiltrate of lymphocytes, plasma cells, and occasional
polymorphonuclear cells. Portions of the parenchyma replaced by
fibrosis,
• Periglomerular fibrosis
• Atrophied tubules with Leukocyte and hyaline casts

 Management :
• Treating infection, if present; ( prolonged AB)
• Preventing future infections; and
• Monitoring and preserving renal function.
Antimicrobial prolonged
Underlying renal
Nephrologic and urologic evaluation

Xanthogranulomatous
Pyelonephritis
• A rare, severe, chronic renal infection typically resulting in
diffuse renal destruction.
• Unilateral nonfunctioning, enlarged kidney associated with
obstructive uropathy secondary to nephrolithiasis.
• Characterized by accumulation of lipid-laden foamy macrophages
• It begins within the pelvis and calyces and subsequently extends
into and destroys renal parenchymal and adjacent tissues.
• It has been known to imitate virtually every other inflammatory
disease of the kidney, as well as renal cell carcinoma, on
radiographic examination

 Pathogenesis :
• Nephrolithiasis(1ry factor) → obstruction + infection →
tissue destruction and collections of lipid material by macrophages .
• These macrophages (xanthoma cells) are distributed in sheets
around parenchymal abscesses and calyces and are intermixed with
lymphocytes, giant cells, and plasma cells.
• Other possible interrelated factors include:
Venous occlusion and hemorrhage,
Abnormal lipid metabolism,
Lymphatic blockage,
Failure of antimicrobial therapy in UTI,
Altered immunologic competence,
Renal ischemia

 Histology :
The parenchyma contains dark
sheets of lipid-laden
macrophages (foamy
histiocytes with small, dark
nuclei and clear cytoplasm)
intermixed with lymphocytes,
giant cells, and plasma cells

Xanthogranulomatous pyelonephritis. A, Gross specimen. Kidney is
massively enlarged, measuring 23 × 12 cm; the normal architecture is
replaced by a shaggy yellow upper pole mass corresponding to
xanthogranulomatous inflammation and numerous distorted and dilated
calyces. B, Microscopically, the shaggy yellow tissue is composed
primarily of lipid-laden histiocytes mixed with other inflammatory cells.
(From Schaeffer AJ: Urinary tract infections

.

 Clinical Presentation :
•
•
•
•

Flank pain (69%),
Fever and chills (69%),
Persistent bacteriuria (46%)
Flank mass (62%)

•

Classic triad :
Unilateral renal enlargement
Poor function
A large calculus in the renal pelvis

 Bacteriology and Laboratory Diagnosis
• Proteus is the most common organism
• Azotemia or frank renal failure is uncommon

• Radiologic Findings :
• CT scan: (most useful)
• A large, reniform mass with the
renal pelvis tightly surrounding a
central calcification but without
pelvic dilatation
•

99mTc-DMSA

:

confirm and quantify the differential
lack of function in the involved
kidney

Xanthogranulomatous pyelonephritis. Enhanced CT scan shows
collecting system and parenchymal calculi (straight arrows) with lower
pole pyonephrosis (curved arrow) and an irregular, predominantly lowdensity perinephric abscess (A) extending into the soft tissues of the
flank

 Management :
• Primary obstacle to treatment of XGP is incorrect diagnosis
XGP + hydronephrosis looks just like pyonephrosis
• Usually post-operative diagnosis
• RCC is usual pre-op diagnosis, so nephrectomy performed
- If localized, may be amenable to partial nephrectomy.
• Xanthoma cells resemble clear cell adenocarcinoma  difficult to
distinguish on frozen section
Do nephrectomy if can't exclude malignancy

• Antibiotics may be necessary to stabilize the patient preop
• If diffuse and extensive disease goes to retroperitoneum, must
remove of the kidney and perinephric fat
- Dissection of granulomatous tissue from the diaphragm, great
vessels, and bowel
- Remove entire mass, as tissue infected in ¾ of pts
• if I&D alone, illness may persist, or develop reno-cutaneous fistula

BACTEREMIA, SEPSIS AND
SEPTIC SHOCK

 Bacteremia:
• The presence of viable bacteria in the blood.
 Systemic inflammatory response syndrome (SIRS):
• Extremes of body temperature, heart rate, ventilation, and immune
response.
• SIRS can occur in response to multiple insults including
systemic infection, trauma, thermal injury or a sterile
inflammation.

 Sepsis:
•

A clinical syndrome characterized by extremes of body
temperature, heart rate, respiratory rate, and WBC count that occurs
in response to an infection.

• Sepsis occurs when a local infectious process becomes an
uncontrolled systemic bloodborne inflammatory response resulting
in damage to tissues or organs remote from the initial site of
infection or injury

 Septic shock:
• An extreme form of sepsis complicated by organ dysfunction and
persistent circulatory failure despite fluid and pharmacologic
resuscitation.

 Pathophysiology:
Bacterial Cell Wall Components in Septic Shock
• The exotoxins (P. aeruginosa)
Bacterial cell wall components → innate immunologic pathways
(macrophages, neutrophils, and dendritic cells and the complement
system).
• The endotoxin (G – tive) :
An LPS component → the coagulation, complement, and
fibrinolytic systems→ release of small molecules that cause

vasodilation and ↑ endothelial permeability

Cytokine Network :
• Monocytic cells have a role in mediation of the biologic effects of
SIRS and septic shock.
• Monocytes can remove and detoxify LPS However, LPS-stimulated
monocytes produce cytokines such as tumor necrosis factor (TNF)
and interleukin (IL)-1.
• The intravascular activation of inflammatory systems involved in
septic shock is mainly the consequence of an overproduction of
these and other cytokines.

 Clinical Presentation and Diagnosis:

• Early signs of the sirs include:
- Temperature extremes (>38° C [100.4° F] or <36° C [96.8 ° F]),
- Tachycardia (heart rate > 90 beats per minute),
- Tachypnea
- Altered mental status.

Characteristics of Sepsis
General

Fever (core temperature >38.3° C)
Hypothermia ( core temperature <36)
Heart rate > 90, 1or 2 SD above the normal value for age.
Tachypnea
Altered mental state
Significant edema or positive fluid balance (20mg\kg over 24h)
Hyperglycemia plasma sugar >120mg\dl or 7.7 mol\l in absence of diabetes

inflammatory

Leukocytosis (WBC count >12,000/μL)
Leukopenia ( WBC count < 4000/µL)
Normal WBC count with >10% immature forms

Organ dysfunction

Arterial hypoxemia (PaO2/FIO2 >300)
Acute oligouria (urine output 0.5 Ml\kg in 1hr for at least 2 hrs)
Creatinine increase 0.5mg\dl
Coagulation abnormalities ( INR 1.5 or aptt >60 sec)
Illus absent bowel sound
Thrombocytopenia ( platelets <100,000µL)
Hyperbilirubinemia ( plasma bilirubin >4mgdl or 70 mmol/L)

Tissue perfusion

Hyperlactatemia (>1 mmol/L)
Decreased capillary refill or mottling

• The classic findings of septic shock :
- Peripheral vasodilation, and ↓ SVR
- A warm patient,
- Brisk capillary refill
- A bounding pulse
- Hypotension, oliguria, or ileus
- ↓↑WBC, hyperbilirubinemia, hyperlactatemia, hyperglycemia,
coagulation abnormalities, and elevated C reactive protein and
respiratory alkalosis due to hyperventilation.

 Bacteriology :
• Gram-negative 30% to 80% of cases mainly E.coli
• Gram-positive 5% to 24% of cases

 Management :
• Resuscitation, vasoactive(phenylephrine)
• Supportive care, monitoring,
• Administration of broad-spectrum antimicrobial agents
(aminoglycoside+/-)
• Antimicrobial treatment should be continued until the patient has
been afebrile for 3 to 4 days and is clinically stable.

 Human activated protein C (Drotrecogin alfa)
• It reduces mortality in sepsis
• An inhibitor of multiple inflammatory and coagulation pathway
components:
The inhibition of the coagulation factors Va and VIIIa,
Inhibition of macrophage production of TNF,
limitation of thrombin-induced inflammation
inhibition of plasminogen activator inhibitor

•

CATHETER-ASSOCIATED
BACTERIURIA

• The most common hospital-acquired infection
• Accounting for up to 40% and ≥1 million per year
• The incidence of bacteriuria :
10% per day of indwelling catheterization.
1% in healthy individuals and 15% in elderly hospitalized
patients for Intermittent catheterization

 risk factors :
•
•
•
•

Duration of catheterization,
Female gender,
Absence of systemic antimicrobial agents,
Catheter-care violations

 Clinical Presentation :
•
•

A symptomatic.
Symptomatic.
Suprapubic discomfort ,fever, chills, or flank pain

 Laboratory Diagnosis
•

Significant bacteriuria if >100 cfu/mL

 Management :
• Careful aseptic insertion of the catheter and maintenance of a
closed dependent drainage system are essential to minimize
development of bacteriuria.
•

The catheter-meatal junction should be cleaned daily with water

• Incorporation of silver oxide or silver alloy into the catheter and
hydrogen peroxide into the drainage bag has been reported to
decrease the incidence of bacteriuria in some studies but not in
other populations.

• Patients with indwelling catheters should only be treated if they
become symptomatic (e.g., febrile).
•

Urine cultures should be performed before initiating antimicrobial
therapy.

• Empirical antimicrobial therapy such as TMP-SMX or a
fluoroquinolone before de-catheterization for 2 days. A post-therapy

• Culture should be obtained 7 to 10 days later to confirm the
eradication of the bacteriuria.
•
•
•

MANAGEMENT OF UTI IN
PATIENTS WITH SPINAL CORD

INJURY

 Epidemiology :
• UTIs are among the most common urologic complications of spinal
cord injury.

• 33% of spinal cord-injured patients have bacteriuria at any time.
• patients on CIC or condom catheterization:
18 episodes of bacteriuria per person per year
1.8 per person per year of febrile UTIs

risk factors
impaired voiding,
overdistention of the bladder,
elevated intravesical pressure,

increased risk of urinary obstruction,
vesicoureteral reflux,
instrumentation
increased incidence of stones.
decreased fluid intake
poor hygiene,
perineal colonization,
local tissue trauma
reduced host defense associated with chronic illness

 Clinical Presentation :
• The majority of patients are asymptomatic
• UTI is the most common cause of fever in spinal cord-injured
• Flank, back, or abdominal discomfort, leakage between
catheterizations, increased spasticity, malaise, lethargy, and/or
cloudy, malodorous urine.

 Bacteriology and Laboratory Diagnosis
•
•
•

Urinalysis : bacteriuria and pyuria.
E. coli is isolated in approximately 20% of patients.
Enterococci, P. mirabilis, and Pseudomonas are more common
among spinal cord-injured patients than patients with intact spinal
cords.
• Other common organisms are Klebsiella species, Serratia species,
Staphylococcus, and Candida species.

•

 Management :
urine culture must be obtained before initiating empirical therapy.
(diverse flora + resistance)

UTI in Pt with spinal cor injury

Febrile UTI

Afebrile UTI

admitted and treated with
a parenteral
aminoglycoside and a
penicillin or a thirdgeneration cephalosporin
for24-48 h

No clinical improvement

- reculture and adjustment
of antimicrobial therapy
- imaging
- urodynamic

- oral fluoroquinolone
- β-Lactams, TMP-SMX, and
nitrofurantoin are not
recommended because of
bacterial resistance

clinical improvement

An indwelling catheter
should be change

 The virulence factor that is most important for
adherence is :
ABCDE-

hemolysin
K antigin
pilli
colicin production
O serogroupe

 The most accurate test for evaluation of infection in
the kidney is :
ABCDE-

the fairly bladder washout test
ureteral catheterization
gallium scanning
CT
the Antibody-coated bacteria test

 The most common bacterial cause of
xanthogranulomaous pyelonephritis is :
ABCDE-

Echerichia coli.
Pseudomonas.
Klebsiella.
Proteus mirabillis.
Staphylococcus.

 Antimicrobial prophylaxis for transurethral resection
of prostate is not indicated in patients with :
ABCDE-

valvular heart disease .
prosthetic valves .
unknown urine culture .
sterile urine .
indwelling catheter .

 The optimal duration of antimicrobial therapy for
symptomatic acute uncomplicated cystitis in women
is :
ABCDE-

1 day.
3 days.
7 days.
14 days.
21 days.

 The drug thought to be safe in any phase of
pregnancy is :
ABCDE-

a fluoroquinolone.
nitrofurantoin.
a sulfonamide.
penicillin.
tetracycline.

Thank you